Captopril, 1-[(2S)-3-mercapto-2-methyl-1-oxopropyl]-L-proline, is an angiotensin converting enzyme inhibitor approved for use as an antihypertensive agent for the treatment of congestive heart failure. Other indications are currently being evaluated.
Captopril is available in the United States from E. R. Squibb & Sons, Inc., in a tablet form in amounts of 12.5 mg., 25 mg., 50 mg., and 100 mg. of active ingredient. In addition, the combination of captopril and hydrochlorothiazide is available in the United States from E. R. Squibb & Sons, Inc. in tablets containing 25 mg. of captopril and 15 mg. or 25 mg. of hydrochlorothiazide and tablets containing 50 mg. of captopril and 15 or 25 mg. of hydrochlorothiazide.
In addition, captopril is available in Japan from Sankyo in a capsule containing an oil formulation of captopril which includes a fatty acid and ascorbic acid.
Joshi et al. in U.S. Pat. No. 4,808,413 disclose a controlled release formulation in the form of beadlets of a medicament such as captopril. The beadlets are formed of the medicament, a non-lipophilic binder-excipient, and an organic carboxylic acid such as citric acid at from at least 5%, preferably at least 10%, by weight of the formulation. The beadlets may also optionally include one or more auxilliary binders, one or more fillers or excipients, one or more lubricants, water, and/or other conventional additives.
Drost et al. in U.S. Pat. No. 4,756,911 disclose a controlled release formulation in the form of a coated tablet containing a core portion from which medicament is slowly released. The core includes hydroxypropylmethyl cellulose having a particular methoxyl content and viscosity as the primary gelling agent. Suitable medicaments are disclosed as including angiotensin converting enzyme inhibitors such as captopril.
Mehta et al. in U.S. Pat. Nos. 4,728,512 and 4,794,001 disclose formulations providing three distinct releases of medicament. The formulation consists of three groups of spheroids containing an active medicinal substance. The first group of spheroids is uncoated and rapidly disintegrates upon ingestion to release an initial dose of medicinal substance a second group of spheroids is coated with a pH sensitive coat to provide a second dose and a third group of spheroids is coated with a pH independent coat to provide a third dose. A powder blend of active medicinal substance may be substituted for the first group of uncoated spheroids. The therapeutic preparation may be utilized as a mixture of groups of spheroids in a capsule.